crossing96/oncoscreening huggingface dataset:
CENPF overexpression in bladder cancer cells enhances proliferation, migration, invasion, and apoptosis.	Bladder cancer has been considered as one of the most common urinary malignancies. Growing evidence has indicated that Centromere Protein F (CENPF) is a promising molecular biomarker for many human malignant tumors. However, the role of CENPF in bladder cancer (BC) proliferation, migration, invasion, cell cycle and apoptosis thereof remain unclear. In the present study, high-throughput sequencing technology and bioinformatics analysis were conducted to identify mRNAs profiles in 10 pairs of bladder cancer tissues and adjacent noncancerous tissues. CENPF was overexpression in bladder cancer tissues, and higher in MIBC than NMIBC. We investigated the expression of CENPF in 30 other pairs bladder cancers tissues, and the results were in accordance with the sequencing results. Furthermore, Immunohistochemical staining, showed that strong intensity of CENPF in BC tissues than normal tissues. Increased staining of CENPF was detected of tumor cells in MIBC compared with NMIBC. This suggests that CENPF might be highly expressed in aggressive and invasive tumor cells. Subsequently, in vitro functional experiments also demonstrated that the siRNA interference of CENPF expression significantly weakened the proliferation, migration, invasion and apoptosis of BC cells, and the cells were arrested in the G2/S phase in Cell cycle. Moreover, functional enrichment analyses, lncRNA-miRNA-mRNA, and protein-protein interaction networks revealed that CENPF was potentially involved in carcinogenesis and evolution of bladder cancer. Taken together, these results demonstrated that CENPF may serve as a potential biomarker of tumor occurrence, progression, and even prognosis for bladder cancer. However, further research is needed to be further clarified the pathway mechanisms of CENPF in bladder cancer.	bladder
Traditional and next-generation bacillus Calmette-Guérin based treatment strategies for bacillus Calmette-Guérin unresponsive non-muscle-invasive bladder cancer in the era of emerging therapies.	PURPOSE OF REVIEW: Bacillus Calmette-Guérin (BCG) remains the standard of care for high-risk non-muscle-invasive bladder cancer (NMIBC), yet up to 40-50% of patients experience treatment failure, leaving limited alternatives to avoid radical cystectomy. This narrative review critically examines both traditional and emerging BCG-based strategies - including repeat induction and modern combination regimens - for patients with BCG-unresponsive NMIBC. RECENT FINDINGS: BCG monotherapy after BCG failure has shown limited effectiveness, with recent studies reporting 12-month disease-free survival (DFS) rates of 60-70%. Nonetheless, BCG continues to serve as an immunotherapeutic backbone in combination strategies. Chemo-immunotherapy regimens, particularly those using gemcitabine or mitomycin C, have achieved 1-year DFS rates of up to 80%. Combinations with cytokines and immunocytokines - such as interferon-α or nogapendekin alfa inbakicept-pmln (NAI) - have demonstrated DFS rates of 45-61%, and NAI has recently received FDA approval. Immune checkpoint inhibitors (e.g., pembrolizumab, durvalumab, atezolizumab) in combination with BCG have shown DFS rates ranging from 42 to 73% at 12 months. However, many studies are limited by small sample sizes and heterogeneous designs. SUMMARY: Despite its limited efficacy as monotherapy in unresponsive cases, BCG retains therapeutic relevance as part of combination strategies that enhance its immunologic activity. Emerging data suggest that these BCG-based regimens offer a promising, bladder-sparing alternative for patients who are ineligible for or decline radical cystectomy. Ongoing and future trials will be essential to define optimal combinations and identify which patients are most likely to benefit, thereby enabling appropriate patient selection.	bladder
Cistanoside F acts as a Monoacylglycerol Lipase inhibitor that synergizes the anti-tumor effect of 2-Arachidonoyl Glycerol on Bladder cancer.	BACKGROUND: Bladder cancer (BCa) remains clinically challenging due to high recurrence rates. As an endocannabinoid, 2-arachidonoylglycerol (2-AG) plays a pivotal role in regulating numerous physiological and pathological processes, including tumorigenesis. The maintenance of its levels in the biological system is essential for 2-AG to exert its biological functions. Therefore, inhibitors targeting the 2-AG metabolic enzyme, such as monoacylglycerol lipase (MGLL), are considered promising for clinical application. METHODS: The cell viability assay, colony formation, cell migration, and invasion assay were used to demonstrate 2-AG's anti-proliferative and anti-metastatic effects in BCa cells, inversely correlated with MGLL expression. MGLL overexpression or knockdown confirmed its regulatory role in 2-AG efficacy. Transcriptomics identified LKB1 as a potential 2-AG target. From a medicinal-food compound library, the MGLL activity assay was used to discover Cistanoside F (CF) as a potent MGLL inhibitor. RESULTS: The in vitro experiments confirmed 2-AG's selective anti-proliferative and anti-metastatic effects in BCa cells, while MGLL attenuates the anti-tumor effect of 2-AG in BCa cells via metabolizing 2-AG into AA. In mechanism, 2-AG activated the LKB1-AMPKα-mTOR axis to suppress BCa progression. At non-cytotoxic concentrations (4-8 nM), CF enhanced 2-AG's effects in BCa cells by sustaining endogenous 2-AG levels through MGLL suppression. In vivo, CF synergized with 2-AG to significantly inhibit tumor growth and lung metastasis compared to 2-AG monotherapy. CONCLUSION: These findings establish CF as a novel MGLL-targeting adjuvant that amplifies 2-AG's anti-BCa efficacy via LKB1 pathway activation, providing dual therapeutic strategies: MGLL inhibition for 2-AG potentiation and LKB1 modulation for pathway-directed therapy.	bladder
Long-term Trends in Bladder Cancer Incidence Using a Harmonized Staging Variable: A SEER-Based Study.	BACKGROUND: Coding changes in disease definitions have influenced trends in bladder cancer epidemiologic outcomes in registries. The Surveillance, Epidemiology, and End Results (SEER) Program introduced a harmonized staging variable (available from the SEER Program upon request) for long-term trend analysis. This study analyzes trends in bladder cancer incidence using the harmonized staging variable. METHODS: Using SEER 12 registry data, we compared trends in the incidence of bladder cancer cases diagnosed from 1992 to 2019 using the revised (or harmonized) staging variable against the original staging variables (SEER modified AJCC third edition for 1992-2003, Derived AJCC sixth edition for 2004-2015, Derived SEER Combined for 2016-2017, and Derived EOD 2018 for 2018-2019). We used joinpoint regression to analyze changes in trends. RESULTS: The data availability has improved with the revised staging system as the proportion of cases with missing lymph node and metastasis stages was substantially reduced. However, the trends varied by tumor stages between the two systems. There were generally more discontinuities in trends with the original system than with the revised system. Unlike the trend observed with the original staging system, the harmonized staging system has shown a 4% annual decrease in Tis incidence since 1992. CONCLUSIONS: With the revised variable, we observed a consistent decrease in the incidence of Tis cases, and the trends seem smoother. IMPACT: Our study highlights the benefits of using revised staging variables to reveal previously hidden patterns, supporting the use of new variables for a more nuanced understanding of temporal trends in epidemiology.	bladder
Development and Utilization of a Novel Electronic Health Record-Based Care Pathway for Nonmuscle-Invasive Bladder Cancer.	INTRODUCTION: Adherence to clinical practice guidelines for nonmuscle-invasive bladder cancer (NMIBC) remains suboptimal. We aimed to develop an electronic health record (EHR)-integrated intervention to improve compliance with clinical guidelines for the management of NMIBC. METHODS: We designed an EHR-integrated intervention within the Epic EHR (Epic Systems) based on the AUA NMIBC pathways. Our multidisciplinary group created 4 pathways for the clinical management of NMIBC: Evaluation and Staging, Low and Intermediate Risk, High and Very High Risk, and Persistent or Recurrent Disease. Adoption was encouraged through a communication strategy including newsletters, site visits, and continuing medical education-accredited meetings. RESULTS: From October 2021 to May 2024, the Care Pathway was used 412 times across various encounter types, including procedural, office-based, and telemedicine visits, involving 253 patients (mean age: 70 years). Self-pay (84; 33.2%) and Medicare (66; 26.1%) were the most common payer type. Sixty-eight providers used the pathway, most commonly by medical doctors (38; 55.9%) and registered nurses (14; 20.6%). The pathway was used primarily in the urology specialty (28; 41.8%), but utilization also occurred in the primary care setting. The initial staging and treatment of low and intermediate risk pathway was the most used Care Pathway (150; 36.4%). CONCLUSIONS: The EHR-integrated intervention was designed to improve adherence to AUA NMIBC guidelines across diverse clinical scenarios and was adopted by providers with varying expertise. This pathway could improve standardized care delivery and reduce practice variability in NMIBC management. Further evaluation of its long-term impact on clinical outcomes is warranted.	bladder
Small cell carcinoma with rhabdomyosarcomatous differentiation of the urinary bladder: an integrated clinicopathological and molecular characterization of five cases.	This study delineates the clinicopathological and molecular features of five rare cases of small cell carcinoma (SmCC) of the urinary bladder with rhabdomyosarcomatous differentiation, distinguishing them from alveolar rhabdomyosarcoma (ARMS). All patients were adult males (median age: 67 years) presenting with hematuria and solitary exophytic bladder masses (mean size: 2.9 cm). Histologically, tumors exhibited predominant SmCC morphology with focal anaplastic features. Focal area showing features suggesting rhabdomyosarcomatous differentiation included scattered cells with eosinophilic cytoplasm and eccentric nuclei resembling rhabdoid or immature skeletal muscle (2/5), and pseudoglandular/alveolar growth patterns mimicking ARMS (2/5). All tumors had coexisting urothelial carcinoma components (accounting for 5-15% of tumor volume). Immunohistochemistry revealed epithelial (AE1/AE3, CAM5.2), neuroendocrine (synaptophysin and/or chromogranin A, INSM1, CD56), and myogenic (desmin, MyoD1, myogenin) marker co-expression within SmCC. Molecular profiling demonstrated universal TP53/RB1 inactivation (5/5), recurrent TERT promoter mutations (4/5), and high tumor mutational burden (mean: 27.4 muts/Mb), while fluorescence in situ hybridization demonstrated the absence of ARMS-defining rearrangements involving PAX3, PAX7, and FOXO1 in all cases. Among four patients with available follow-up (5-19 months), one died of disease at 5 months, one developed multiple bone metastases by 5 months, while two showed no tumor recurrence or metastatic progression (both were treated with radical cystectomy followed by adjuvant etoposide-cisplatin chemotherapy). This study provides the first integrated clinicopathological and molecular characterization of SmCC with rhabdomyosarcomatous differentiation in the bladder. The presence of SmCC-specific alterations (TP53/RB1/TERT) and absence of ARMS-defining fusions support classification as a unique SmCC subtype with divergent rhabdomyosarcomatous differentiation.	bladder
Impact of regular cystoscopy on prognosis in non-muscle-invasive bladder cancer: A nationwide study.	PURPOSE: Transurethral resection of bladder tumors (TUR-BT) requires follow-up evaluation by cystoscopy. We sought to evaluate the prognosis of non-muscle-invasive bladder cancer (NMIBC) patients within 6 months of surgery to identify the optimal timing for the first cystoscopy after TUR-BT. MATERIALS AND METHODS: In this retrospective analysis, patients newly diagnosed with NMIBC were divided into two groups according to whether they underwent cystoscopy within 6 months after TUR-BT. We considered four outcomes: recurrence, progression, cancer-specific mortality, and all-cause mortality. Inverse probability treatment weighting (IPTW)-adjusted Kaplan-Meier analysis was performed to identify the difference in survival for each outcome stratified by cystoscopy status within 6 months after the first TUR-BT. We employed Cox regression models with IPTW to estimate the hazard ratios (HRs) of each outcome according to cystoscopy status. RESULTS: Among 40,678 patients, 11,940 (29.4%) did not undergo cystoscopy within 6 months. The risk of recurrence was higher for patients who underwent cystoscopy than those who did not (HR 1.32, 95% confidence interval [CI] 1.26-1.38, p<0.001). By contrast, the cystoscopy group had a lower risk of progression compared to the non-cystoscopy group (HR 0.70, 95% CI 0.65-0.76, p<0.001), with lower cancer-specific mortality (HR 0.62, 95% CI 0.56-0.68, p<0.001) and all-cause mortality (HR 0.58, 95% CI 0.56-0.60, p<0.001). CONCLUSIONS: Cystoscopy within 6 months was associated with a higher risk of recurrence but a lower risk of progression and death. Therefore, regular cystoscopy after the first TUR-BT for NMIBC is essential to ensure favorable survival outcomes.	bladder
Causal role of phenylalanine and cholesterol metabolism in bladder cancer Chemoresistance: Insights from mendelian randomization and targeted molecular docking.	Bladder cancer (BLCA) exhibits profound chemoresistance, partly mediated by metabolic dysregulation. This study investigated the roles of phenylalanine (Phe) and cholesterol metabolism in BLCA chemoresistance using integrated omics and computational modeling. Transcriptomic analysis of the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets revealed that elevated hexokinase 2 (HK2) and low-density lipoprotein receptor (LDLR) expression correlates with poor response to cisplatin. Mechanistically, Phe catabolism via phenylalanine hydroxylase (PAH) activated mTORC1 signaling, promoting glycolysis and drug efflux, while cholesterol biosynthesis driven by SREBP2 enhanced ABCG2 transporter activity. Mendelian randomization (MR) analyses confirmed causal associations between Phe/cholesterol metabolism and chemoresistance risk. Pharmacological inhibition of HMG-CoA reductase or dietary phenylalanine restriction sensitized BLCA cells to cisplatin both in vitro and in xenograft models. Overexpression of FOLH1 or F7 reversed the inhibitory effects of Phe or cholesterol targeting, respectively, confirming their functional roles in resistance. These findings identify FOLH1 and F7 as mediators of metabolic resistance in BLCA and suggest metabolic targeting as a promising therapeutic strategy. However, whether combined inhibition of Phe and cholesterol pathways provides synergistic benefits over monotherapy remains to be determined in future studies.	bladder
mTORC1 Selective Nano-Inhibitor by Disrupting the Lysosomal Arginine-SLC38A9- mTORC1-CDKs Axis for Precision Bladder Cancer Therapy.	The absence of precise targeting and defined mechanisms, akin to small molecules, remains a major barrier to the clinical translation of nanomedicines. Mammalian target of rapamycin complex 1 (mTORC1), a key regulator of cell proliferation and metabolism, is linked to abnormal activation in various diseases like cancers. While small-molecule inhibitors of mTORC1 are limited, they remain a focus. Here, a strategy is presented for mTORC1-specific nano-inhibitors targeting the lysosomal arginine (Arg)-SLC38A9-mTORC1 pathway. Using [2Fe-2S]CO(6) as a universal paradigm, nanomedicines are developed (e.g., ZnPc-SFeCO) that degrade Arg in the lysosome, inhibiting SLC38A9 activation and blocking mTORC1 recruitment. ZnPc-SFeCO inhibits mTORC1 at ultra-low concentrations (1.07 ng mL(-1)), with three orders of magnitude greater specificity than the clinical small molecule rapamycin. SLC38A9 knockout abolishes nanomedicine efficacy. Differential responses to the inhibitors are also observed in normal and bladder cancer cells, linked to SLC38A9 expression levels, suggesting potential for precise treatment of non-muscle invasive bladder cancer (NMIBC). In vivo, ZnPc-SFeCO combined with photodynamic therapy outperformed MMC in preventing tumor recurrence and extending survival. This work establishes a promising approach for developing mTORC1-specific nano-inhibitors with well-defined targets and mechanisms, offering new insights into the development of precision nanomedicines for cancer therapy.	bladder
Disease burden of bladder cancer in China and the different SDI regions over the world from 1990 to 2021.	Bladder cancer is the most prevalent malignancies in the urinary system. This study was designed to investigate the trends of bladder cancer in China and differences compared with various Socio-demographic index (SDI) regions. Data from the Global Burden of Disease (GBD) 2021 database were utilized to evaluate metrics associated with bladder cancer, including age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life years rate (DALY) (ASDR). All analyses, including joinpoint regression, age-period-cohort, decomposition, spearman correlation, frontier and cross-country inequality, and Bayesian age-period-cohort, were utilized. In 2021, bladder cancer posed a significant health burden in China, with 570,636 total cases, including 463,364 males. The disease burden increased from low to high SDI regions, with China falling in the middle to high-middle SDI range. Apart from China, middle SDI and low-middle SDI regions, the ASIR of all other SDI regions showed a decreasing trend. The ASPR of bladder cancer increase globally, particularly in China and middle SDI region. Meanwhile, the ASMR and ASDR declined in China and all SDI regions. The age-period-cohort analysis showed that period and cohort effects influenced the ASIR and ASPR differently across China and each SDI region. Population growth was the primary driver of increases in these metrics. Projections suggest continued increases in ASIR, ASPR, and ASDR for both genders in China through 2036. The burden of bladder cancer is significant in China and varies across SDI regions, highlighting the link between socioeconomic development and disease burden.	bladder
PKIB facilitates bladder cancer proliferation and metastasis through mediation of HSP27 phosphorylation by PKA.	Cyclic AMP-dependent protein kinase A (PKA) is recognized for its pivotal involvement in various cancer types, with Protein Kinase Inhibitor Beta (PKIB) serving as an endogenous inhibitor that curtails PKA activity. Despite the documented escalation of PKIB expression in several malignancies, a comprehensive understanding of its precise mechanistic implications in human cancers remains elusive. This investigation is centered on bladder cancer (BLCA), unveiling an augmented expression of PKIB concomitant with heightened BLCA cell proliferation, migration, and invasion in vitro and augmented tumorigenic potential in an in vivo model. Mechanistically, PKIB disrupts PKA kinase activity, thereby resulting in diminished phosphorylation of the substrate target protein HSP27 at serine 15, 78, and 82. Additionally, the transcription factor MYCN exhibits an affinity for the PKIB promoter, leading to its enhanced expression in the context of BLCA. These findings reveal the oncogenic proclivity of PKIB and introduce a novel signalling pathway in BLCA, providing valuable insights into potential therapeutic targets for precise intervention.	bladder
Effect of Sex Differences on Cancer Outcomes After Chemo-Radiation for Muscle-Invasive Bladder Cancer: A Retrospective Multicenter Cohort Study.	OBJECTIVE: To examine whether the well demonstrated sex-based differences in bladder cancer management and outcomes are similarly observed for those treated with chemo-radiation for muscle invasive bladder cancer (MIBC). METHODS: This retrospective, multicenter study reports on patients who underwent curative intent radiotherapy, with concurrent chemotherapy, for MIBC across 10 academic centers in Canada. The primary outcome was cancer specific survival (CSS) and secondary outcomes included complete response and overall survival (OS). Survival was estimated using the Kaplan-Meier method. Multivariable regression models were performed to assess an independent association of sex on outcomes. RESULTS: There were 397 males and 145 females who underwent curative intent chemo-radiation for MIBC with a total median follow-up of 30 months. Baseline cancer characteristics and treatment specifics were similar between the sexes, although complete resection was more common in males and hydronephrosis was more common in females. There were no differences in complete response rates between males and females (72.3% vs 73.1%). The 3-year CSS was 78.4% vs 70.4% for males and females respectively and median OS was 81 months vs 52 months. Cumulative incidence of mortality was similar between the sexes with organ-confined disease but higher for females with non-organ-confined disease. In multivariable analysis, sex was independently associated with CSS (HR 1.46, 95% CI 0.95-2.24) but not OS. CONCLUSION: This multicenter study demonstrated worse CSS in females undergoing chemo-radiation. Future investigations should explore potential effects from differences in staging, as well as other biological- and treatment-related factors, including differential responses to chemo-sensitized radiation.	bladder
The effect of race/ethnicity on systemic chemotherapy in urothelial carcinoma patients exposed to radiotherapy.	INTRODUCTION: Based on prospective trials' result, it is unknown whether race/ethnicity affects the magnitude of cancer-specific survival differences after trimodal therapy (TMT) versus external beam radiation therapy alone (EBRT) for urothelial carcinoma for urinary bladder (UCUB). We addressed this knowledge gap. MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified patients with cT2-T4aN0M0 UCUB treated with either TMT or EBRT. We focused on the four most prevalent race/ethnicities: Caucasians, Hispanics, African American (AAs) and Asian/Pacific Islanders (APIs). Cumulative incidence plots and multivariable competing risks regression (CRR) models addressed cancer specific mortality (CSM) after additional adjustment for other-cause mortality (OCM) and standard covariates. RESULTS: Of 3249 patients, 2643 (81%) were Caucasians versus 254 (8%) AAs versus 209 (7%) Hispanics versus 143 (4%) APIs. Compared to EBRT, TMT rates were higher in Caucasians (81%) and APIs (81%), lower in AAs (75%) and lowest in Hispanics (69%). In Caucasians, five-year CSM rates were 41.6% after TMT versus 49.0% after EBRT and TMT independently predicted lower CSM (HR: 0.70, p < 0.001). In AAs, Hispanics and APIs, TMT did not predict CSM differences (p = 0.1, 0.2 and p = 0.06, respectively). CONCLUSION: For Caucasians UCUB patients, TMT is strongly associated with significantly lower CSM. However, this observation cannot be generalized non-Caucasian subgroups, where TMT did not predict lower CSM relative to EBRT.	bladder